About 34.3 million adults are currently living with HIV/AIDS. The predominant mode of HIV transmission worldwide is through heterosexual contact. Although many factors are associated with sexual transmission of HIV-1 (both behavioral and biologic), HIV-1 viral load has been identified as the chief predictor of the risk of sexual transmission. Levels of HIV-1 viral load have been associated with mother-to-infant transmission of HIV. Several studies have also shown a good correlation between blood plasma viral load and male and female genital tract viral load. The use of antiretoviral medications can reduce blood plasma HIV-1 RNA levels as well as genital tract HIV-1 RNA. Studies have also shown a reduction in perinatal transmission with effective antiretroviral therapy. Transmission of drug resistant HIV-1 has been reported in the US and Europe ranging from 2% to 27% among newly infected patients. There have been reports of resistant genotypic variants in both male and female genital tract that is different from those of blood. These findings underscore the risk of spreading resistant HIV-1 variants sexually as well as perinatally. Understanding the dynamics of HIV-1 in the genital tract is of great importance in strategies to control sexual and perinatal transmission of HIV. The specific aims of this study are: 1) To understand the dynamics of viral failure and viral replication in the femal genital tract, 2) To assess drug exposure and patterns of drug resistance in the female genital tract and 3) To evaluate latent reservoirs in the female genital tract. To address issues of viral failure, development of resistance and drug levels, we will enroll 50 HIV(+) women who are failing their current antiviral regimen. We will assess paired plasma and genital tract secretions at multiple time points for: viral load, genotyping, and peak and trough drug levels before and after changing therapy. To evaluate latent reservoirs in the genital tract, we will enroll 50 HIV(+) women who are fully suppressed on antiviral therapy and propose to collect endocervical cells by a swab/cytobrush technique in an attempt to recover replication competent virus. We also propose to enroll women who have undergone total hysterectomy to assess HIV dynamics in the vagina.